Manufacture of salicylic acid glycerin esters.



.15 hereafter.

CARL SORGER, OF FRANKFQRT-ON-THE-MAIN, GERMANY.

MANUFACTURE OF SALIGYLIC ACID GLYCERIN ESTERS.

Specification of Letters Patent.

Patented March 24, 1908 Application filed. January 14, 1907. SerialNo..352,261. (Specimena) To all whom it may concern:

Be it known that I, CARL SORGER, a subject of the German Emperor, and aresident of Frankfort-on-the-Main, Germany, have invented certain newand usefulImprovements in the Manufacture of Salicylic Acid Glycerin.Esters, of which the following is a Specification.

My invention relates to improvements in .10 the manufacture of salicylicacid glycerin esters and to the new product produced thereby, whichprocess broadl consists in .heating alph l esters of salicy ic acid withglycerin, an in certain details set forth By said new process a productof valuable thera eutic roperties is duced' which can e use as an antireumati'c and an antiseptic particularly for external use. Theproductanswers the follow-' ingformulaz- OH o\ 011,000 0 o n drron mo cntershasrheretofore received but little attention, and such substitutionas has been pro- .posed related merely to esters the acids of whichbelong to the fat series. It has been found, that alcohols of highervalence and polyatomic univalent -alcohols in esters can e replaced byalcohols of lower atomicit applicable.

formic acid brenzracemic ester with methy alcohol described by L. Henry(Bulletin 1 Acad. Roy. 'Belpigae 1902, 445 and Gentralblatt 1902 I p.928) fail; when applied 4 to heating acetic acid brenzracemic ester withmethyl alcohol. Furthermore, in the German Patent No. 99,057 (ExampleZ),a process has been described which consists in replacing, in a carbonicacid ester having one alcohol radical and one henol radical,

the said alcohol radical by t e corresponding phenol radical by means ofthe action of one phenol. However, the substitution of one aliphaticalcohol radical by another one in esters of aromatic acids has not yetbecome known. Now, I have found, that by heating the salicylic. acidethyl ester with glycerin a salicylic acid glycerin esterof hi htherapeutical properties is obtained. T e reaction takes place in such away that the alcohol of low atomicity is separated from the ester bydistillation and is replaced by an alcohol of higher valenc and higheratomicity, viz. the glycerin. he process is therefore inverse to that ofthe esters of the fatseries referred to above.

The exchange of the alcohol in my new process of producing glycerinester is effected 111 the same manner, as for example in the case of theeasily separable acid esters of the phenols, as has been found with thesalicylic acid phenyl ester, or salol (see German Patent No, 111,656).However, the reaction referred to in the said patent can also notuniversally be carried out as indicated in said patent; thereforefurther investigations were necessary in each case.

My new process Involves an lmprovement in the process of roducingsalicylic acid glycerin esters described in the German Patents Nos.126,311 and 127,139, because the raw material used is cheaper, the herrice-of I the alphyl esters of salicylic aci use in my 1 process instead'of the salicylic acid used in The substitution of one alcohol radicalby 30 another one in esters for producing new 68-.

the process referred to being more than compensated, by the expense forthe much,

greater quantity of glycerin required .in the processes knownheretofore. And on the other hand it is not necessary in my process toisolate the product of the reaction. The resultof the reaction, viz. theroduction of salicylic acidglycerin ester cou d not 'be anticipatedbecause the glycerin, as is well known, is decomposed at highertemperatures (formation of acrolein), and the same is the case withsalicylic acid when heated above its melting oint. The substitution ofthe methyl alco 01 in my process when heated with glycerin is effectedmore speedily than that of ethyl alcohol. The reactlon 1s romoted byusing a small amount of hyrate of sodium or of sodium salts, such as.the carbonate, acetate, salicylate, on account First example: 100 partsof salicylic acid methyl ester and 120 parts of glycerin together with0.2 arts of acetate of sodium are heated gradually up to 195 centigrade,when a milk-like liquid is distilled off which consists of water and asmall quantity of ester. When the said temperature has been reached theliquids which before were separated, commence gradually to combine in ahomogeneous liquid, and the alcohol commences to distil ofi (alsocarrying with itself a small quantity of methyl ester). The methylalcohol in the distillate may alter rectification be used again for themanufacture of salicylic acid methyl ester. When the distillation of thealcohol begins, the temperature is gradually raised within 24 hours to215 centigrade until no more alcohol distils off. The oily product ofreaction is poured into hot water in order to isolate the glycerinester. After the solution has re mained in an unheated condition for awhile the ester separates almost wholly in crystalline form, but it mayalso be separated from the watery solution by means of ether. Whencrystallized again from the ether it forms fine white needles the proerties of which are the same as those of t e known monosalicylicacid-glycerin ester.

Second example: 100 parts of salicylic acid ethyl ester and 120 parts ofglycerin are treated in the same way as in Example I whereby theethyl-alcohol is distilled off. The further steps of the process are thesame as in the preceding example.

The process described in the examples is illustrated by the followingequation:

OH OH The product of the reaction, viz., the monosalicylic-acid glycerinester, the formula of which is stated above, crystallizes into whiteneedles the melting point of which is between 74 and 76 centigrade. Coldwater dissolves but small proportions thereof, viz. only 1 per cent,while hot water dissolves it esaeao easily. The same applies to benzoland petroleum ether. It is easily soluble in glycerin and alcohol, alittle less in ether. It is easily separated into its components byalkalies and carbonates of allialies. The crystals are inodorous andhave a bitter taste. The product is used as an antirheumatic and anantiseptic especially for external use, as its oily solution intoglycerin and alcohol is easily absorbed by the skin.

I claim:

1.. The herein described process of producing a salicylic acid glycerinester, which consists in heating a mixture of an alphyl ester ofsalicylic acid and glycerin to a temperature at which. the alcohol setfree is distilled oil, and isolating the glycerin ester from the oilyproduct of reaction by the addition of a non-solvent.

2.. The herein described process of producing a salicylic acid glycerinester, which consists in heating a mixture of an alphyl ester ofsalicylic acid and glycerin to a temperture at which the alcohol setfree is distilled off, and isolating the glycerin ester from the oilyproduct of reaction by the ad dition of cold water.

3. The herein described process of producing a salicylic acid glycerinester, which consists in heating a mixture of an alphyl ester ofsalicylic acid and glycerin to a temperture at which the alcohol setfree is distilled oft, isolating the glycerin/ ester from the oilyproduct of reaction by means of cold water and separating the same fromits solution in Water by the addition of ether.

4. The herein described process of producing a salicylic acid glycerinester, which consists in heating a mixture of an alphyl ester ofsalicylic acid, glycerin and a sodium compound to a temperature at whichthe alcohol set free is distilled off, and isolating the glycerin esterfrom the oily product of reaction by the addition of a non-solvent.

In testimony whereof I have signed my name to this specification in thepresence oi two subscribing witnesses.

' CARL SORGER.

Witnesses:

FRANZ HASSLACI-IER, MIcHAEL V0LK.

